Polymorphisms in Iron Homeostasis Genes and Urinary Cadmium Concentrations among Nonsmoking Women in Argentina and Bangladesh.
(2013) In Environmental Health Perspectives 121(4). p.467-472- Abstract
- BACKGROUND: Cadmium (Cd) is a human toxicant and carcinogen. Genetic variation might affect long-term accumulation. Cadmium is absorbed by iron transporters. OBJECTIVES: To evaluate the impact of iron homeostasis genes (divalent metal transporter 1 SLC11A2; transferrin TF; transferrin receptors TFR2 and TFRC; ferroportin SLC40A1) on Cd accumulation. METHODS: Subjects were non-smoking women living in the Argentinean Andes [n=172; median urinary Cd (U-Cd)=0.24 µg/L] and Bangladesh (n=359; U-Cd=0.53 µg/L) with Cd exposure mainly from food. U-Cd and Cd in whole blood or erythrocytes (Ery-Cd) was measured by ICPMS. Fifty polymorphisms were genotyped by Sequenom. Gene expression was measured in whole blood (n=72) with Illumina DirectHyb... (More)
- BACKGROUND: Cadmium (Cd) is a human toxicant and carcinogen. Genetic variation might affect long-term accumulation. Cadmium is absorbed by iron transporters. OBJECTIVES: To evaluate the impact of iron homeostasis genes (divalent metal transporter 1 SLC11A2; transferrin TF; transferrin receptors TFR2 and TFRC; ferroportin SLC40A1) on Cd accumulation. METHODS: Subjects were non-smoking women living in the Argentinean Andes [n=172; median urinary Cd (U-Cd)=0.24 µg/L] and Bangladesh (n=359; U-Cd=0.53 µg/L) with Cd exposure mainly from food. U-Cd and Cd in whole blood or erythrocytes (Ery-Cd) was measured by ICPMS. Fifty polymorphisms were genotyped by Sequenom. Gene expression was measured in whole blood (n=72) with Illumina DirectHyb HumanHT-12 v4.0. RESULTS: TFRC rs3804141 was consistently associated with U-Cd. In the Andeans, mean U-Cd concentrations were 22% (95% CI: -2, 51%) and 56% (95% CI: 10, 120%) higher in women with GA and AA genotypes, respectively, relative to women with the GG genotype. In Bangladesh, mean U-Cd concentrations were 22% (95% CI: 1, 48%) and 58% (95% CI: -3, 157%) higher in women with GA and AA versus GG genotype, respectively (adjusted for age and plasma ferritin in both groups; p for trend 0.006 [Andes] and 0.009 [Bangladesh]). TFRC expression in blood was negatively correlated with plasma ferritin (rS=-0.33, p=0.006), and positively correlated with Ery-Cd (significant at ferritin concentrations <30 µg/L only, rS=0.40, p=0.046). Rs3804141 did not modify these associations or predict TFRC expression. Cd was not consistently associated with any of the other polymorphisms evaluated. CONCLUSIONS: One TFRC polymorphism was associated with urine Cd concentration, a marker of Cd accumulation in the kidney, in two very different populations. The consistency of the findings supports the possibility of a causal association. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3559677
- author
- Rentschler, Gerda LU ; Kippler, Maria ; Axmon, Anna LU ; Raqib, Rubhana ; Ekström, Eva-Charlotte ; Skerfving, Staffan LU ; Vahter, Marie and Broberg Palmgren, Karin LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Environmental Health Perspectives
- volume
- 121
- issue
- 4
- pages
- 467 - 472
- publisher
- National Institute of Environmental Health Sciences
- external identifiers
-
- wos:000323706100031
- pmid:23416510
- scopus:84875876181
- pmid:23416510
- ISSN
- 1552-9924
- DOI
- 10.1289/ehp.1205672
- language
- English
- LU publication?
- yes
- id
- 714618d7-d038-4b2d-b02e-89cdc0b50535 (old id 3559677)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23416510?dopt=Abstract
- date added to LUP
- 2016-04-01 10:34:32
- date last changed
- 2022-01-26 00:33:51
@article{714618d7-d038-4b2d-b02e-89cdc0b50535, abstract = {{BACKGROUND: Cadmium (Cd) is a human toxicant and carcinogen. Genetic variation might affect long-term accumulation. Cadmium is absorbed by iron transporters. OBJECTIVES: To evaluate the impact of iron homeostasis genes (divalent metal transporter 1 SLC11A2; transferrin TF; transferrin receptors TFR2 and TFRC; ferroportin SLC40A1) on Cd accumulation. METHODS: Subjects were non-smoking women living in the Argentinean Andes [n=172; median urinary Cd (U-Cd)=0.24 µg/L] and Bangladesh (n=359; U-Cd=0.53 µg/L) with Cd exposure mainly from food. U-Cd and Cd in whole blood or erythrocytes (Ery-Cd) was measured by ICPMS. Fifty polymorphisms were genotyped by Sequenom. Gene expression was measured in whole blood (n=72) with Illumina DirectHyb HumanHT-12 v4.0. RESULTS: TFRC rs3804141 was consistently associated with U-Cd. In the Andeans, mean U-Cd concentrations were 22% (95% CI: -2, 51%) and 56% (95% CI: 10, 120%) higher in women with GA and AA genotypes, respectively, relative to women with the GG genotype. In Bangladesh, mean U-Cd concentrations were 22% (95% CI: 1, 48%) and 58% (95% CI: -3, 157%) higher in women with GA and AA versus GG genotype, respectively (adjusted for age and plasma ferritin in both groups; p for trend 0.006 [Andes] and 0.009 [Bangladesh]). TFRC expression in blood was negatively correlated with plasma ferritin (rS=-0.33, p=0.006), and positively correlated with Ery-Cd (significant at ferritin concentrations <30 µg/L only, rS=0.40, p=0.046). Rs3804141 did not modify these associations or predict TFRC expression. Cd was not consistently associated with any of the other polymorphisms evaluated. CONCLUSIONS: One TFRC polymorphism was associated with urine Cd concentration, a marker of Cd accumulation in the kidney, in two very different populations. The consistency of the findings supports the possibility of a causal association.}}, author = {{Rentschler, Gerda and Kippler, Maria and Axmon, Anna and Raqib, Rubhana and Ekström, Eva-Charlotte and Skerfving, Staffan and Vahter, Marie and Broberg Palmgren, Karin}}, issn = {{1552-9924}}, language = {{eng}}, number = {{4}}, pages = {{467--472}}, publisher = {{National Institute of Environmental Health Sciences}}, series = {{Environmental Health Perspectives}}, title = {{Polymorphisms in Iron Homeostasis Genes and Urinary Cadmium Concentrations among Nonsmoking Women in Argentina and Bangladesh.}}, url = {{https://lup.lub.lu.se/search/files/1958028/3789314.pdf}}, doi = {{10.1289/ehp.1205672}}, volume = {{121}}, year = {{2013}}, }